The goal of this study is to determine if carriers of the gene for familial medullary carcinoma of the thyroid (MCT) can be distinguished from non-carriers by cytogenetic testing. Analyses have been completed on seven family members ranging in age from 38 to 62 with histologically proven MCT and on two low-risk individuals. The spouses of these individuals served as age-and environmentally-matched controls. Additional controls consisted of five local, healthy volunteers ranging in age from 28 to 55. Seventy-two hr PHA-stimulated lymphocyte cultures were performed, and all slides were coded and scored blindly. For each individual, 150 conventionally stained metaphases were examined for chromatid and chromosome breaks and rearrangements. Fifty G-banded metaphase spreads were scored for aberrations and 25 of these 50 were completely analyzed. PHA-stimulated cultures were also harvested without exposure to colchicine or hypotonic solution, and 100 mitotic figures scored for segregational errors of chromosomes. Prophase banding was also performed. The results of prophase banding analysis were inconclusive. Results of the other parameters studied showed no differences between MCT patients and the controls. Our results may or may not be in conflict with those studies that have described chromosome instability in MEN II families, since our family so far displays only familial MCT and not the full MEN II syndrome inclusive of pheochromocytomas and hyperparathyroidism. These studies will now be expanded for comparative purposes to include two additional families; one of these repesents the full MEN II syndrome, whereas the status of the other is as yet unclear. Tests will include clastogenic challenge by bleomycin of cells from affected and control individuals in an effort to detect by exaggeration any intrinsic instability that is too low to detect in a small sample by the normal cytogenetic analysis. Thus analyses for affected and control members of each family will include high resolution prophase banding and karyotypic analysis and breakage studies with and without clastogen. Excluded will be analysis of segregational errors of chromosomes and study of low risk/no risk family members and young children. (Q)